Doctor, it helps when I do this …

By Dale Bredesen, M.D., Chief Scientific Officer for Apollo Health

As we’ve found again and again over the years, for any of us who have cognitive complaints, there are almost always multiple contributors, whether it’s metabolic syndrome or sleep apnea or an undiagnosed infection or any of many other potential drivers. However, in many people, there is a rate-limiting contributor, one that must be included in the personalized protocol (and preferably the main focus) if cognitive improvement is to occur.

Some people are particularly adept at noticing which treatments lead to large improvements and which produce little or no change, and this observational skill is associated with better outcomes. Therefore, it’s valuable to look at what the implication is for each of the outsized responses. As an example, one common response is when someone receives intravenous glutathione (often with PC, phosphatidylcholine) and has a dramatic improvement, which typically lasts until the next day. This strongly implicates toxicity as the rate-limiting driver of the cognitive decline (and raises the question of whether there may be some degree of Lewy body disease), and thus directs us to look carefully at all potential toxins and ensure that we optimize the detoxification in order to achieve the best cognitive outcome.

In contrast, other individuals will notice the greatest impact with EWOT (exercise with oxygen therapy), which implicates energetics, and specifically cerebral blood flow and/or oxygenation, as the rate-limiting contributors. This pushes us in a very different direction for optimal outcomes.

A third scenario involves individuals who experience a marked improvement with BHRT (bioidentical hormone replacement), demonstrating that their endogenous hormones are suboptimal. This dramatic response is typically observed with toxin-induced cognitive decline (progesterone is important in detox), often with stress (due to pregnenolone steal, in which pregnenolone is shunted away from sex hormones and into stress hormones), and sometimes with energetic reduction (estradiol is a key player in cerebral energetic support). It is usually straightforward to determine which of these three possibilities is the rate-limiting contributor, simply by looking at the setting and the hormonal status.

There are a number of situations in which such marked symptom amelioration occurs, so it behooves all of us to be keen observers and diligent history takers. Here are several more such circumstances:

Responding well to exogenous ketones implicates energetic failure, usually associated with metabolic dysfunction and its attendant insulin resistance. Similarly, an excellent response to creatine (5-20g/day) also implicates energetic support as the rate-limiting driver.

Occasionally, as noted first by Julie G, someone will have a dramatic response to Nurtec ODT or Ubrelvy, both of which are CGRP inhibitors typically used for migraine headaches. However, in the setting of cognitive decline, this response points to mast cell activation as a key contributor.

A striking response to HBOT (hyperbaric oxygen) typically implicates vascular insufficiency or traumatic brain injury as critical contributors.

LDN is another therapeutic that creates a marked response in some individuals, and this implicates autoimmunity — not simply inflammation from an innate immune response, but an adaptive immune response that targets an antigen with cross-reaction with an autoantigen in the brain.

For the many people diagnosed with sleep apnea, some will notice virtually no benefit with CPAP, whereas others will experience marked cognitive improvement, and once again, this will indicate which people have sleep apnea (or in some cases, UARS, upper airway resistance syndrome) as a rate-limiting driver of cognitive decline.

Some will notice marked improvements when they travel, whereas others notice decline when they travel (one woman had been doing very well until her son made the college football team, and she started overnight travel each week, reinitiating decline): for those with improvement, mycotoxins due to moldy homes are the usual culprit, and for those who decline with travel, stress is the implicated factor, which often ties to toxin exposure.

Another common scenario is a marked improvement on starting the protocol and including the KetoFLEX 12/3 diet, accompanied by weight loss of 20-40 pounds. Since there are several benefits of KetoFLEX 12/3, such as metabolic flexibility, anti-inflammation, and detoxing fiber, this may implicate metabolic syndrome, gut leakiness, or some toxin exposure.

Sometimes people note marked improvement with antibiotic use, while in other cases, the antibiotic use is associated with decline. In the former situation, the implication is infections such as tick-borne illness like Borrelia or Babesia or Bartonella. In the latter situation, mitochondrial damage, exacerbated by antibiotics, is implicated.

Yet another scenario features marked improvement after treatment with Dentalcidin or Stella rinse, along with oral probiotics. This of course implicates oral dysbiosis, often with P. gingivalis (which is strongly associated with Alzheimer’s) or T. denticola or F. nucleatum.

Noticing any of these enhanced responses, and discussing them with your practitioner, is very helpful toward achieving optimal outcomes. Furthermore, noticing an oversized negative response can also be helpful in implicating a key driver of decline.

It is common to see marked decline with a urinary tract infection (and these are often missed until they are severe), and this implicates inflammation as a key driver.

Marked decline following COVID-19, which is common, usually implicates microthrombi and mitochondrial function, but in some cases may also implicate autoimmunity.

Chemical sensitivity — to perfumes or laundry detergent or any of many other chemicals — implicated Bartonella infection or mycotoxins, as pointed out by Dr. Neil Nathan, an expert in chemical sensitivity (his excellent book, The Sensitive Patient’s Healing Guide, goes into detail on this).

Exercise-induced exhaustion and decline implicate mitochondrial damage, and fasting-associated decline implicates frailty, often associated with malabsorption and the need for digestive enzymes and gut healing.

As we learn more and more about the key elements leading to cognitive decline, we are able to focus more rapidly on the most important inducers, and achieve better and better outcomes, with fewer and fewer failures. I look forward to the day when we are able to treat everyone with cognitive decline successfully — it is such a blessing to see people regain their sharpness, personalities, and purpose.